Administration of anti-inflammatory steroids results in profound effects on collagen metabolism. The effect of this class of therapeutic agents on collagen metabolism may be affected by decreasing prolyl hydroxylase. This enzyme is responsible for the hydroxylation of certain prolyl residues in collagen peptides to form hydroxyproline, an amino acid found almost exclusively in collagen. Administration of triamcinolone diacetate to rats results in a decrease of prolyl hydroxylase. Treatment with anti-inflammatory steroids may ultimately result in either secretion of underhydroxylated collagen, a decreased secretion of collagen and (or) a feedback inhibition of collagen polypeptide synthesis, if indeed prolyl hydroxylase is the rate limiting enzyme in collagen biosynthesis. Studies done thus far and future investigations are aimed at determining the importance of glucocorticoid mediated alteration of the prolyl hydroxylase in the overall effects of this class of drugs on collagen metabolism in both normal and diseased tissues. We propose to determine the effects of glucocorticoids (using the synthetic steroid traimcinolone as a model compound) on the synthesis, secretion and degradation of collagen. Since the collagen produced during drug treatment is only a very small percent of that already laid down as part of the extracellular matrix, it will be necessary to study the biosynthetic capacity and physical properties of collagen produced by steroid treated cells in an extracellular matrix free cell system. Furthermore studies will be carried out to determine molecular mechanisms of alterations of prolyl hydroxylase and possibly collagen polypeptide synthesis. Thus in the future we may initiate studies to either block or mimic the effects of this class of drugs on collagen metabolism.